The Ac2-26 peptide of ANXA1 protects against sepsis-induced acute kidney
injury by negatively regulating the PI3K/IKK/NF-κB pathway
Abstract
BACKGROUD AND PURPOSE The aim of the present study was to explore the
effects of annexin A1 (ANXA1) mimetic peptide AC2-26 on sepsis-induced
acute kidney injury by negatively regulating the PI3K/IKK/NF-κB pathway
in vivo and in vitro and the underlying mechanisms. EXPERIMENTAL
APPROACH In vivo, a mouse model was established by cecal ligation and
puncture (CLP), and the Ac2-26 peptide of ANXA1 (1 mg/kg) was
intraperitoneally administered 2 hours before CLP. In vitro, A model of
HK-2 cells was established by treatment with 10 μg/ml lipopolysaccharide
(LPS), and the Ac2-26 peptide of ANXA1 (0.5 μmol/L) was administered 2
hours before LPS. The kidney function of mice detected by Elisa. The
kidney tissue was examined by HE and TEM. The inflammatory cytokines and
apoptotic molecules were measured by PCR, Elisa, Western blotting and
Immunohistochemistry. The apoptosis was detected by TUNEL and flow
cytometry. KEY RESULTS The studies demonstrated that ANXA1 markedly
improved kidney function and kidney tissue injury and enhanced 7-day
survival in CLP-induced septic mice, which was accompanied by a
significant decrease the inflammatory molecules. ANXA1 obviously
downregulated the apoptosis-associated proteins and inhibited apoptosis
in kidney tissue in vivo. In vitro studies showed that ANXA1 increased
the viability of HK-2 cells, reduced the levels of the inflammatory
molecules, downregulated the apoptosis-associated proteins Bax,
upregulated the antiapoptotic protein Bcl-2 and inhibited the apoptosis
of HK-2 cells. CONCLUSION AND IMPLICATIONS These results demonstrate
that ANXA1 is a potential chemotherapeutic agent against septic AKI
through negative regulation of the PI3K/IKK/NF-κB pathway.